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First published online 15 March 2006
doi: 10.1242/dev.02329

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Zinc-finger gene Fez in the olfactory sensory neurons regulates development of the olfactory bulb non-cell-autonomously

Tsutomu Hirata^1,*, Masato Nakazawa¹, Sei-ichi Yoshihara², Hitoshi Miyachi³, Kunio Kitamura⁴, Yoshihiro Yoshihara² and Masahiko Hibi^1,

¹ Laboratory for Vertebrate Axis Formation, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
² Laboratory for Neurobiology of Synapse, Brain Science Institute, RIKEN, Wako-shi, Saitama 351-0198, Japan.
³ Laboratory for Animal Resources and Genetic Engineering, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
⁴ Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan.

Author for correspondence (e-mail: hibi{at}cdb.riken.jp)

Accepted 16 February 2006

Fez is a zinc-finger gene encoding a transcriptional repressor that is expressed in the olfactory epithelium, hypothalamus, ventrolateral pallium and prethalamus at mid-gestation. To reveal its function, we generated Fez-deficient mice. The Fez-deficient mice showed several abnormalities in the olfactory system: (1) impaired axonal projection of the olfactory sensory neurons; (2) reduced size of the olfactory bulb; (3) abnormal layer formation in the olfactory bulb; and (4) aberrant rostral migration of the interneuron progenitors. Fez was not expressed in the projection neurons, interneurons or interneuron progenitors. Transgene-mediated expression of Fez in olfactory sensory neurons significantly rescued the abnormalities in olfactory axon projection and in the morphogenesis of the olfactory bulb in Fez-knockout mice. Thus, Fez is cell-autonomously required for the axon termination of olfactory sensory neurons, and Fez non-cell-autonomously controls layer formation and interneuron development in the olfactory bulb. These findings suggest that signals from olfactory sensory neurons contribute to the proper formation of the olfactory bulb.

Key words: Fez, Zinc finger, Olfactory sensory neuron, Olfactory bulb, Axon guidance, Mitral cell, Interneuron, Rostral migratory stream, Mouse

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